Recently, it has been found that in the differentiation of undifferentiated pluripotent hemopoietic stem cells to mature blood cells, a number of hemopoietic factors are mutually involved In various levels and thus a complicated hemopoietic network system is formed. Furthermore, most of the hemopoietic factors are being genetically cloned and several hemopoietic factors are being mass produced by genetic recombination techniques, and their clinical applications are in progress. On the other hand, although pluripotent hemopoietic stem cells are characterized by their self-replicating ability (growth), sufficient studies have not been done on the growth factors which affect the undifferentiated pluripotent hemopoietic stem cells in the bone marrow.
It is known that bone marrow stromal cells play a major role in the growth of the pluripotent hemopoietic stem cells and their differentiation into mature cells; some kind of fluid factors secreted by the stromal cells, or intercellular reactions or the like are thought to be involved in hemopoieses in the bone marrow.
For example, it is known that bone marrow stromal cell line MC3T3-G2/PA-6(PA-6) which is established from the calvaria of C57B1/6 newborn mouse supports the growth of mouse pluripotent hemopoietic stem cells (Kodama, H. et al., J. Cell. Physiol., 112, 89, 1982).
In recent years, a ligand for a c-kit protein, which is a tyrosine kinase receptor being expressed in pluripotent stem cells, has attracted attention as a factor involved in the growth of undifferentiated stem cells and great efforts have been made to substantiate the ligand; in 1990, three research groups succeeded in genetically cloning the ligand. They were reported as SCF (stem cell factor; K. M. Zsebo et al., Cell, 63, 195-201, 1990), MGF (mast cell growth factor; D. E. Williams et al., Cell, 63, 167-174, 1990) and KL (c-kit ligand; Huang et al., Cell, 63, 225-233, 1990).
At present, the mechanism of the action of the ligand is being studied using the c-kit ligand which is mass produced by genetic recombination techniques and studies to date are clarifying that this factor acts on the stem cells which are differentiated to a certain extent (Hayashi et al., Int. J. Hematology, Suppl. No. 1, p198, 1991).
Accordingly, it is now considered that aside from this protein, other factors exist which act on pluripotent hemopoietic stem cells which are differentiated to a lesser extent in the bone marrow.
The hemopoietic factors having the above-mentioned activities can be made into useful pharmaceuticals such as therapeutic agents to restore bone marrow growth after the use of anti-cancer agents or after bone marrow transplantation and therapeutic agents for bone marrow malfunctions such as hypoplastic anemia and osteomyelodysplasia syndrome.
Furthermore, the hemopoietic factors having the above-mentioned activities can be used as a useful reagent or the like for in vitro proliferation of peripheral stem cells and bone marrow stem cells and furthermore as an analytical reagent or as an antigen for preparation of antibodies.